Biomedical Engineering Reference
In-Depth Information
ear. This fact plus the ease with which defects in bundle orientation can be
discerned and quantified has made the inner ear one of the best and most
heavily studied examples of vertebrate PCP. Moreover, the recent demon-
stration that elongation of the cochlear duct is also regulated by the PCP
pathway has provided an additional aspect of inner ear development that
can be examined in terms of the roles of different PCP molecules
( Montcouquiol et al., 2003; Wang, Hamblet, et al., 2006 ). In this review,
we provide a general overview of the development of the inner ear, with
a primary focus on the mammalian system, followed by a more detailed
description of the roles of different PCP molecules and how these factors
interact at a molecular level
to mediate both elongation and bundle
orientation.
2. DEVELOPMENT OF THE INNER EAR
In all vertebrates, the inner ear develops predominantly from the otic
placode, a thickening of the dorsal ectoderm located adjacent to the devel-
oping hindbrain (reviewed in Driver & Kelley, 2009; Puligilla & Kelley,
2009 ). The placode undergoes a period of proliferation, sinks inwards
toward the hindbrain, and constricts at the ectodermal surface to
eventually pinch off and form a fluid-filled otocyst. Formation of the
otocyst is followed by a series of elaborate morphogenetic changes that
result in the development of the various structures within the inner ear.
In mammals, the cochlear duct begins as a ventral out pocketing from the
otocyst that extends and coils over time. The epithelial cells that line the
otocyst and all of its derivatives give rise to both the sensory patches
containing mechanosensory hair cells and supporting cells and the
nonsensory cells that comprise the remainder of the inner ear.
In mouse, outgrowth of the cochlea begins around E11 and continues
through the early postnatal period ( Fig. 5.1 ). Within the duct, individual
cells that will develop as hair cells can first be identified between E13 and
E15. As these cells differentiate from surrounding progenitor cells, a period
of cellular rearrangement and patterning occurs that leads to the develop-
ment of a highly ordered pattern of both hair cells and supporting cells that
is completed by approximately postnatal day 0 (P0) ( McKenzie, Krupin, &
Kelley, 2004 ). Two types of hair cells, inner and outer hair cells, as well as at
least six different types of supporting cells are arranged into ordered rows that
extend along the basal-to-apical axis of the entire cochlear spiral. During the
same developmental time period, several patches of hair cell-containing
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